The United States is one of the top nations for prematurely born infants and has a correspondingly high day- one infant mortality rate. Expanding our understanding of alveologenesis is a critical step toward promoting proper lung formation in preterm infants. This, however, remains an unsolved challenge as no systematic study of the molecular components of normal lung development during late term and early childhood has previously been conducted. For this reason, NHLBI is establishing four research centers to develop a molecular atlas of the developing lung (LungMAP). In response to this call, we have assembled a research team with the necessary experience to successfully establish a molecular atlas of the mouse and human lung based on spatial imaging and cell-specific -omic technologies. Within organs such as the lung, the relationship between space, anatomy, and function is fundamental. Therefore, our approach will include imaging techniques with high spatial resolution, as well as cell-specific -omics. The future correlation of these complementary data collection methods will facilitate the establishment of cell-specific spatial informatics acros the developing lung. Specifically, we will accomplish our goal of an integrated molecular atlas of lung development through the following aims: (1) Spatial imaging for a molecular atlas of the developing mouse and human lung (2) Cell type- specific omics for a molecular atlas of the developing mouse and human lung (3) Manage data and metadata to facilitate collaboration and data integration. Overall, these aims will create the first spatial-temporal molecular atlas of the mammalian lung during alveologenesis, which in coordination with the other LungMAP centers will provide an unprecedented array of information about the healthy developing lungs in mouse and human. The novel imaging approaches and the suite of integrated pan-omics capabilities (i.e. proteomics, lipidomics, metabolomics and activity-based protein profiling) developed and available in a single laboratory at PNNL represents a unique strength of the Research Center.
The goal of this research project is to create a detailed map of how the healthy lung changes in humans during the four months before birth until two years of age. This map will include enhanced views of cells and the molecules inside the cells, across the different functional components of the lung. Understanding how the healthy lungs develop is critical to increasing our understanding of disrupted lung development in preterm infants, so that we can learn to mitigate or prevent significant adverse health outcomes in the future.
|Dautel, Sydney E; Kyle, Jennifer E; Clair, Geremy et al. (2017) Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung. Sci Rep 7:40555|
|Rindler, Tara N; Stockman, Courtney A; Filuta, Alyssa L et al. (2017) Alveolar injury and regeneration following deletion of ABCA3. JCI Insight 2:|
|Kochen, Michael A; Chambers, Matthew C; Holman, Jay D et al. (2016) Greazy: Open-Source Software for Automated Phospholipid Tandem Mass Spectrometry Identification. Anal Chem 88:5733-41|
|Clair, Geremy; Piehowski, Paul D; Nicola, Teodora et al. (2016) Spatially-Resolved Proteomics: Rapid Quantitative Analysis of Laser Capture Microdissected Alveolar Tissue Samples. Sci Rep 6:39223|